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Genetic factors are assumed to contribute to memory performance, especially genes affecting the dopaminergic neurotransmission. We aimed to evaluate leading functional genetic variants of the dopamine system, Catechol-O-methyltransferase (COMT) SNP rs4680 and Brain-derived neurotropic factor (BDNF) SNP rs6265, previously found to be associated with memory performance. In two independent general population cohorts (total N = 5937) we investigated direct and interaction effects between COMT and BDNF SNPs on declarative memory performance. We found significant two-way interactions for COMT and BDNF in both cohorts but no direct genetic effects. Sensitivity analyses revealed that an interaction between COMT and BDNF was mainly carried by females. While direct associations of COMT and BDNF on memory have been reported previously, we could demonstrate that the interaction of COMT and BDNF is sex-dependent and more complex and needs further investigation. Our results could be demonstrated in two independent cohorts of valuable size.

Objective Alexithymia is associated with various mental as well as physical disorders. Some evidence also suggested high alexithymia to increase mortality risk, but these results are few and based on specific sample compositions. We aimed to investigate the impact of alexithymia on mortality risk in a large population based cohort. In addition, we sought to elucidate the effects of the subfactors of alexithymia and sex differences. Methods In a sample of N = 1380 individuals from the Study of Health in Pomerania (SHIP), we investigated the hazard-ratio (HR) of alexithymia as obtained by the Toronto Alexithymia Scale-20 (TAS-20) on all-cause mortality over an average observation time of 10 years. Sex-by-TAS-20-interactions as well as sex-stratified analyses were performed. Results Alexithymia was significantly associated with enhanced mortality risk (HR = 1.033; 95%-CI = 1.008–1.058); p = 0.009). While sex-by-TAS-20 interactions remained insignificant, sex-stratified analyses showed that this effect was only significant in men (HR = 1.050; 95%-CI = 1.022–1.079; p ≤ 0.001), but not in women (HR: 1.008; 95%-CI = 0.960–1.057; p = 0.76). The effect was validated for the “difficulties identifying feelings” (DIF) and “difficulties describing feelings” (DDF) subfactors of the TAS-20. Conclusion Our study supports and extents previous findings by indicating that mortality risk enhancing effects of alexithymia are specific to male subjects and validated for the DIF and DDF facets. Socioeconomic, clinical and metabolic factors were associated with this relationship. Finding that the impact of alexithymia remains stable in the fully adjusted models suggests that yet unidentified additional factors must be considered.

Introduction Insufficient vitamin D levels were found to be related to various psychiatric disorders and particularly depression. The functional polymorphisms rs4588 and rs7041 of the vitamin D‐binding protein (also group‐specific component or Gc) influence vitamin D level and activity. Resilience is considered the individual predisposition to maintain psychological functioning in the face of adversities. We sought to investigate whether associations of vitamin D levels and genotypes of rs4588 and rs7041 were associated with trait resilience and symptoms of depression. Methods Serum levels of total 25(OH)D were measured in a general population sample (n = 1,908) of the Study of Health in Pomerania (SHIP‐1). The Resilience Scale‐25 (RS‐25) was applied to assess trait resilience. Lifetime depressive symptoms were assessed using the CID‐S, while current depressive symptoms were measured using the Beck Depression Inventory II (BDI‐II). Study participants were genotyped for rs4588 and rs7041. Results Participants with vitamin D insufficiency had lower adjusted mean RS‐25 scores as compared to vitamin D replete subjects (p = .002). Linear regression analyses revealed a positive association between 25(OH)D and RS‐25 scores (ß = 2.782, p = .002). Additional adjustment for BDI‐II scores slightly attenuated this result (ß = 1.830 and p = .026). Symptoms of depression and the lifetime diagnosis of MDD were not significantly associated with vitamin D concentrations. rs4588 and rs7041 showed strong associations with vitamin D concentrations (both p, We found that resilience, but not depression, was strongly associated with vitamin D levels in 1,908 subjects from the general population. The association with resilience remained stable after adjustment for depressive symptoms. Functional polymorphisms of the vitamin D‐binding protein gene (rs4588 and rs7041) were highly associated with vitamin D levels, but neither depression nor resilience.

Inflammaging describes the complexity between low-grade chronic inflammation with the pathogenesis of brain aging and Alzheimer´s disease (AD). We aimed to find associations of inflammatory markers: i) white blood cell count (WBC), ii) high-sensitivity C-reactive protein (hs-CRP), and iii) fibrinogen with brain structures, sensitive neuroimaging markers of advanced brain aging and AD-like atrophy, and cognitive aging scores. We analyzed magnetic resonance imaging (MRI) scans of 2204 participants from the Study of Health in Pomerania-2 (SHIP-2) and SHIP-Trend (55.6% women, mean age 52.4±13.7 years). Associations of the inflammatory markers with specific brain signatures of brain aging (SPARE-BA), AD-like brain atrophy (SPARE-AD) and white matter disease (white matter hyperintensities volume (WMHV)) were investigated. Furthermore we explored their association with general brain structures including total brain volume (TBV), gray matter volume (GMV), and white matter volume (WMV), as well as cognitive scores (Nurnberger Age Inventory (NAI); Verbal Learning and Memory Test (VLMT). We adjusted for multiple vascular risk factors (VRF; e.g. smoking and blood pressure) and corresponding medication use to take their brain aging effects into account and corrected for false-discovery rate (FDR). Results:WBC was inversely associated with SPARE-BA (FDR-adjusted p=0.003), TBV (FDR-adjusted p=0.019) and GMV (FDR-adjusted p= 0.017). GMV was also inversely associated with hs-CRP (FDR-adjusted p=0.039) and fibrinogen (FDR-adjusted p=0.039). None of the inflammatory markers was associated with WMHV. Regression analysis also revealed a trend-level interaction between intake of antiinflammatory medication and hs-CRP with brain aging (SPARE-BA; FDR-adjusted p=0.062). Inflammatatory markers are associated with neuroimaging markers, with elevated WBC leading to significant acceleration in brain aging patterns but not with AD-like imaging structural changes. Given the overlap between accelerated brain aging and AD-like atrophy, increased WBC might be associated with global dementia symptoms due to this overlap in atrophy patterns. Elevated WBC may be not causal to preclinical AD dementia, but an accessory symptom of inflammaging. At population level, our results support the relevant roles of inflammatory markers on brain aging related atrophy.

Background The mineralocorticoid receptor (MR) in the brain has a key role in the regulation of the central stress response and is associated with memory performance. We investigated whether the genetic polymorphisms rs5522 and rs2070951 of NR3C2 showed main and interactive effects with childhood trauma on memory decline. Methods Declarative memory was longitudinally assessed in 1,318 participants from the community‐dwelling Study of Health in Pomerania using the Verbal Learning and Memory Test (VLMT). In a subsample of 377 participants aged 60 and older, the Mini‐Mental Status Examination (MMSE) was additionally applied. Mean follow‐up time for the VLMT and MMSE were 6.4 and 10.7 years, respectively. Results Homozygous carriers of the G allele of rs2070951 (p, The mineralocorticoidreceptor has a central role in the brains stress response. In this longitudinal general population study, we investigated whether rs5522 and rs2070951 of the MR gene are associated with memory performance. Using two different measures for memory performance, we found that these single nucleotide polymorphisms were associated with diminished declarative memory decline.

A complex interplay between genetic and environmental factors determines the individual risk of depressive disorders. Vitamin D has been shown to stimulate the expression of the tryptophan hydroxylase 2 (TPH2) gene, which is the rate-limiting enzyme for serotonin production in the brain. Therefore, we investigate the hypothesis that serum vitamin D levels moderate the interaction between the serotonin transporter promotor gene polymorphism (5-HTTLPR) and childhood abuse in depressive disorders. Two independent samples from the Study of Health in Pomerania (SHIP-LEGEND: n = 1 997; SHIP-TREND-0: n = 2 939) were used. Depressive disorders were assessed using questionnaires (BDI-II, PHQ-9) and interview procedures (DSM-IV). Besides serum vitamin D levels (25(OH)D), a functional polymorphism (rs4588) of the vitamin D-binding protein is used as a proxy for 25(OH)D. S-allele carriers with childhood abuse and low 25(OH)D levels have a higher mean BDI-II score (13.25) than those with a higher 25(OH)D level (9.56), which was not observed in abused LL-carriers. This significant three-way interaction was replicated in individuals with lifetime major depressive disorders when using the rs4588 instead of 25(OH)D (p = 0.0076 in the combined sample). We conclude that vitamin D relevantly moderates the interaction between childhood abuse and the serotonergic system, thereby impacting vulnerability to depressive disorders.

Low levels of vitamin D were found to be associated with different mental disorders. However, the role of vitamin D in the pathogenesis of PTSD is unclear. In this study, we aimed at investigating whether PTSD is linked to reduced vitamin D levels and vitamin D deficiency. Moreover, we sought to investigate the role of the vitamin D-binding protein (also group-specific component or Gc) by testing if two functional polymorphisms (rs4588 and rs7041) were associated with vitamin D levels and PTSD.Serum levels of total 25(OH)D were measured in a general-population sample of the Study of Health in Pomerania (SHIP-1). The number of traumatic events and status of PTSD were assessed using the PTSD module of the Structured Clinical Interview for the DSM-IV. Study participants were genotyped for rs4588 and rs7041. Associations of 25(OH)D levels and the genotypes with PTSD were tested in subjects with at least one traumatic event (n = 1653).25(OH)D levels were inversely (OR: 0.96; p = 0.044) and vitamin D deficiency was positively (OR = 2.02; p = 0.028) associated with PTSD. Both polymorphisms of the Gc were associated with 25(OH)D levels and PTSD: Carriers of the CC-genotype of rs4588 showed significantly higher 25(OH)D levels (ß = 0.179, p

BackgroundPrevious studies suggested that exposure to traumatic events during childhood and adulthood and post-traumatic stress disorder (PTSD) are associated with a dysregulation of different neuroendocrine systems. However, the activity of the renin–angiotensin–aldosterone-system (RAAS) in relation to trauma/PTSD has been largely neglected.MethodsTraumatization, PTSD, and plasma concentrations of renin and aldosterone were measured in 3092 individuals from the general population. Subgroups according to the status of traumatization (‘without trauma’; ‘trauma, without PTSD’, ‘PTSD’) were formed and compared regarding renin and aldosterone concentrations. Additionally, we calculated the associations between the number of traumata, renin, and aldosterone concentrations. Finally, associations of PTSD with renin/aldosterone levels were controlled for the number of traumata (‘trauma load’).ResultsLevels of renin, but not aldosterone, were increased in traumatized persons without PTSD (p= 0.02) and, even stronger, with PTSD (p< 0.01). Moreover, we found a dose–response relation between the number of traumata and renin levels (β= 0.065;p< 0.001). Regression analyses showed PTSD as a significant predictor of renin (β= 0.38;p< 0.01). This effect was only slightly attenuated when controlled for trauma load (β= 0.32;p< 0.01).ConclusionsOur results suggest that traumatization has lasting and cumulative effects on RAAS activity. Finding elevated renin levels in PTSD independent from trauma load supports the concept of PTSD as a disorder with specific neuroendocrine characteristics. Alternatively, elevated renin levels in traumatized persons may increase the risk for developing PTSD. Our findings contribute to explain the relationship between traumatic stress/PTSD and physical disorders.

Previous evidence suggested lasting and cumulative effects of traumatization on the renin-angiotensin-aldosterone-system (RAAS). However, it is unclear whether traumas during childhood and those experienced in adulthood differentially impact the RAAS. In this study, we sought to investigate main and putative interactive effects of childhood and adulthood trauma on RAAS functioning.Plasma concentrations of renin and aldosterone were measured in a general population sample (n = 2016). Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ), adulthood trauma was measured using the PTSD module of the Structured Clinical Interview of the DSM-IV. Linear regression models were calculated to assess the relations between childhood or adulthood traumatization with renin and aldosterone concentrations.Exposure to (ß = 0.094; p = 0.01), severity of childhood trauma (ß = 0.004; p = 0.01) were associated with increased aldosterone, but not renin levels. Results were carried by all dimensions of abuse, while childhood neglect was not associated with altered RAAS activity. In contrast, adulthood traumas (ß = 0.113; p 0.01) were significantly associated with increased renin concentrations. Subjects with PTSD (renin: ß = 0.345; p = 0.01; aldosterone: ß = 0.232; p = 0.04) and those who had been exposed to both childhood and adulthood trauma showed increases in renin (ß = 0.180; p 0.01) and aldosterone (ß = 0.340; p 0.01) levels.These findings indicate that trauma is associated with differential alterations of the RAAS depending on the time of traumatization. Moreover, exposure to childhood or adulthood trauma may act synergistically on the RAAS, resulting in severe dysregulation of the RAAS. The results contribute to explain associations between trauma and enhanced risk for physical disease.

Background Associations of alexithymia with temporomandibular pain disorders (TMD), facial pain, head pain and migraine have been described, but the role of the different dimensions of alexithymia in pain development remained incompletely understood. Objectives We sought to investigate the associations of alexithymia and its subfactors with signs of TMD and with facial pain, head pain and migraine in the general population. Methods A total of 1494 subjects from the general population completed the Toronto Alexithymia Scale-20 (TAS-20) and underwent a clinical functional examination with palpation of the temporomandibular joint and masticatory muscles. Facial pain, migraine and head pain were defined by questionnaire. A set of logistic regression analyses was applied with adjustment for age, sex, education, number of traumatic events, depressive symptoms and anxiety. Results Alexithymia was associated with TMD joint pain (Odds Ratio 2.63; 95% confidence interval 1.60-4.32 for 61 TAS-20 points vs the median of the TAS-20 score) and with facial pain severity (Odds Ratio 3.22; 95% confidence interval 1.79-5.79). Differential effects of the subfactors were discovered with difficulties in identifying feelings as main predictor for joint, facial, and head pain, and externally oriented thinking (EOT) as U-shaped and strongest predictor for migraine. Conclusion Alexithymia was moderately to strongly associated with signs and symptoms of TMD. These results should encourage dental practioners using the TAS-20 in clinical practice, to screen TMD, facial or head pain patients for alexithymia and could also help treating alexithymic TMD, facial or head pain patients.

Die Langzeitfolgen insbesondere komplexer sequenzieller Realtraumatisierungen haben wegen der mit ihnen verbundenen vielschichtigen Symptomatik zur Entwicklung des Konzepts der sog. komplexen posttraumatischen Belastungsstorung (PTBS) gefuhrt. Diese Storung ist durch anhaltende Veranderungen des affektiven Systems, der Selbstwahrnehmung sowie der interpersonellen und sozialen Beziehungen gekennzeichnet. Die Zahl kontrollierter und randomisierter Studien zur Therapie komplexer PTBS ist relativ gering. Die Ergebnisse dieser Studien zeigen, das traumafokussierte kognitiv-behaviorale Interventionen wirksam sind und gute Effektstarken hervorbringen.

Previous evidence showed associations of alexithymia with altered declarative memory performance. However, these findings were not fully consistent and the underlying mechanism remains unclear. Alexithymic subjects may be at specific risk for chronic psychosocial stress, which in turn represents a predictor for poorer memory performance. We investigated independent and interaction effects of alexithymia and chronic perceived stress on declarative memory performance. Data were used from two independent general-population samples from the Study of Health in Pomerania (SHIP). In sample 1 (N = 1981), the Auditory Verbal Learning Test, the Toronto Alexithymia Scale (TAS-20) and the Screening Scale for Chronic Stress (SSCS) were applied. In sample 2 (N = 3799), the word list of the Nuremburg Age Inventory and TAS-20 were administered to replicate findings. Alexithymia was significantly associated with poorer immediate and delayed word recall. Chronic stress negatively predicted immediate, but not delayed recall. Alexithymia and particularly “Difficulties Identifying Feelings” showed significant associations with chronic perceived stress. Our findings provide clear evidence for an association of alexithymia with impaired declarative memory performance for words. The strong association of alexithymia with perceived chronic stress could contribute to explain the association of alexithymia with stress-related disorders.

Objective Alexithymia, neuroticism, and extraversion have been described as relevant predictors of mental and physical health conditions, but their putative interactive effects remain poorly understood and their prospective effects are not well studied. The present study has investigated the differential contributions of distinct personality traits in predicting mental and somatic health symptoms in cross-sectional and longitudinal analyses. Methods Additive and interactive effects of neuroticism and extraversion (NEO-FFI), the TAS-20 total score (20-Item Toronto Alexithymia Scale) and its factors (Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF) and External Oriented Thinking (EOT)) have been investigated on depressive symptoms, the number of chronic diseases, somatic and mental subjective health complaints. Analyses have been based on data from the population-based “Study of Health in Pomerania” (SHIP) in cross-sectional (N = 1704) and longitudinal (N = 1244) analyses. Results In cross-sectional and longitudinal analyses, additive associations of the TAS-20 total score and neuroticism on somatic and mental health complaints have been observed. The effects of the TAS-20 total score have been mainly carried by DIF. Further, in interaction effetcs extraversion has attenuated the negative impact of neuroticism, whereas DIF has augmented it. Conclusion The present study is the first demonstrating longitudinal effects of alexithymia, particularly DIF, neuroticism, and extraversion in predicting mental and somatic health symptoms. Associations between DIF, neuroticism, and extraversion have been additive and interactive. Hence, subjects high in neuroticism and DIF but low in extraversion have reported most health symptoms and thus might be in need for prevention strategies. Treatments chould be adapted to the associated combination of the personality characteristics.

Serum neuron-specific enolase (sNSE) is considered a marker for neuronal damage, related to gray matter structures. Previous studies indicated its potential as marker for structural and functional damage in conditions with adverse effects to the brain like obesity and dementia. In the present study, we investigated the putative association between sNSE levels, body mass index (BMI), total gray matter volume (GMV), and magnetic resonance imaging-based indices of aging as well as Alzheimer’s disease (AD)-like patterns. Subjects/Methods: sNSE was determined in 901 subjects (499 women, 22–81 years, BMI 18–48 kg/m2), participating in a population-based study (SHIP-TREND). We report age-specific patterns of sNSE levels between males and females. Females showed augmenting, males decreasing sNSE levels associated with age (males: p = 0.1052, females: p = 0.0363). sNSE levels and BMI were non-linearly associated, showing a parabolic association and decreasing sNSE levels at BMI values >25 (p = 0.0056). In contrast to our hypotheses, sNSE levels were not associated with total GMV, aging, or AD-like patterns. Pathomechanisms discussed are: sex-specific hormonal differences, neuronal damage/differentiation, or impaired cerebral glucose metabolism. We assume a sex-dependence of age-related effects to the brain. Further, we propose in accordance to previous studies an actual neuronal damage in the early stages of obesity. However, with progression of overweight, we assume more profound effects of excess body fat to the brain.

Background: Depression and obesity are widespread and closely linked. Brain-derived neurotrophic factor (BDNF) and vitamin D are both assumed to be associated with depression and obesity. Little is known about the interplay between vitamin D and BDNF. We explored the putative associations and interactions between serum BDNF and vitamin D levels with depressive symptoms and abdominal obesity in a large population-based cohort. Methods: Data were obtained from the population-based Study of Health in Pomerania (SHIP)-Trend (n = 3,926). The associations of serum BDNF and vitamin D levels with depressive symptoms (measured using the Patient Health Questionnaire) were assessed with binary and multinomial logistic regression models. The associations of serum BDNF and vitamin D levels with obesity (measured by the waist-to-hip ratio [WHR]) were assessed with binary logistic and linear regression models with restricted cubic splines. Results: Logistic regression models revealed inverse associations of vitamin D with depression (OR = 0.966; 95% CI 0.951–0.981) and obesity (OR = 0.976; 95% CI 0.967–0.985). No linear association of serum BDNF with depression or obesity was found. However, linear regression models revealed a U-shaped association of BDNF with WHR (p < 0.001). Conclusion: Vitamin D was inversely associated with depression and obesity. BDNF was associated with abdominal obesity, but not with depression. At the population level, our results support the relevant roles of vitamin D and BDNF in mental and physical health-related outcomes.

Background: The mechanism of how childhood trauma leads to increased risk for adult dissociation is not sufficiently understood. We sought to investigate the predicting effects and the putatively mediating roles of PTSD and alexithymia on the path from childhood trauma to adult dissociation. Methods: A total of 666 day-clinic outpatients were administered the Childhood Trauma Questionnaire (CTQ), the Toronto Alexithymia Scale (TAS-20), the Posttraumatic Diagnostic Scale (PDS), and the Dissociative Experiences Scale (DES) and controlled for sex, age, and the Global Symptom Index (GSI). Linear regression analyses and mediation analyses were applied. Results: Independent predictive effects on dissociation were found for childhood trauma, alexithymia and PDS, even after adjusting for GSI. Effects of childhood neglect on dissociation were slightly stronger than of abuse. Alexithymia did not mediate the path from childhood trauma to dissociation. Mediation by PDS was specific for childhood abuse, with all PTSD symptom clusters being significantly involved. Conclusions: Childhood abuse and neglect are important predictors of dissociation. While the effects of abuse are mediated by PTSD, the mechanism of how neglect leads to dissociation remains unclear. The results further support the predictive value of alexithymia for adult dissociation above and beyond the effects of childhood trauma, PTSD, and GSI scores.

Background: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions and associated with various psychiatric disorders. Neuroimaging studies found evidence for morphological and functional brain alterations in alexithymic subjects. However, the neurobiological mechanisms underlying alexithymia remain incompletely understood. Methods: We study the association of alexithymia with cortical correlation networks in a large community-dwelling sample of the Study of Health in Pomerania. Our analysis includes data of n = 2,199 individuals (49.4% females, age = 52.1 ± 13.6 years) which were divided into a low and high alexithymic group by a median split of the Toronto Alexithymia Scale. Cortical correlation networks were constructed based on the mean thicknesses of 68 regions, and differences in centralities were investigated. Results: We found a significantly increased centrality of the right paracentral lobule in the high alexithymia network after correction for multiple testing. Several other regions with motoric and sensory functions showed altered centrality on a nominally significant level. Conclusions: Finding increased centrality of the paracentral lobule, a brain area with sensory as well as motoric features and involvement in bowel and bladder voiding, may contribute to explain the association of alexithymia with functional somatic disorders and chronic pain syndromes.